Observations on Leukemia in Wistar and Wistar Furth Rats

1. Six-hundred and seventy-three Wistar and W/Fu rats were treated atthe age of 4 months with whole body x-ray, orally administered 3MCA or acombination of these agents. All animals were followed until death and 87per cent were autopsied.

2. Among 303 autopsied animals there were 403 benign and malignanttumors, including 28 leukemias.

3. Differences were noted in the incidence and types of leukemia occurring in both breeds of rats. In Wistars 9 of 11 leukemias were myelogenous and 8 of these followed x-ray exposure.

4. Approximately a 10 per cent incidence of spontaneously occurring mononuclear cell leukemia was found in W/Fu rats; exposure to x-ray apparentlydecreased the occurrence of leukemia in these rodents. Following oral administration of 3MCA, 13 per cent of W/Fu rats developed acute mononuclear cell leukemia.

5. Results of hematologic, cytologic and histochemical studies on ratleukemia are discussed in this article, and the possible significance of theappearance and disappearance of the distinctive mononuclear cells in theperipheral blood is pointed out.

6. Pathologic findings indicate that the majority of deaths, other than thosedue to leukemia, were due to pulmonary infections and a great variety oftumors. In leukemic animals enlargement of the spleen was almost universally present and adenopathy, especially involving mediastinal and retroperitoneal glands, was frequently noted. Among 9 myelogenous leukemiasin Wistar rats green chloromatous tissues were found in 5 animals.

7. Cytogenetic studies were carried out on direct preparations from thebone marrow in most of the leukemic rats in this series. Aneuploidy wasnoted in several animals and one W/Fu rat demonstrated a morphologicallyabnormal "marker" chromosome. In more recent studies improved technicsand use of the spleen as a source of metaphase preparations have affordedbetter opportunities to obtain adequate chromosome preparations in leukemic rats. Further investigations are in progress and special studies arebeing directed to the viral and cytogenetic aspects of leukemia in the rat.

Submitted on December 4, 1964 Accepted on January 25, 1965     

Asystole with Syncope Secondary to Hyperventilation in Three Young Athletes

We describe three athletes who had syncope after (case 1) or during (cases 2, 3) hyperventilation. During the episode, ECG showed prolonged sinus arrest. Clinical data and noninvasive investigations were normal and the phenomenon was not reproducible. Electrophysiological study after autonomic blockade allowed a prolonged intrinsic heart rate in case 1, and abnormal corrected sinus node recovery time in cases 1 and 2. During follow-up, symptomatic sinus arrest provoked by deep inspiration occurred in case 3. These cases document prolonged asystole of unknown etiology, secondary to hyperventilation, and probably caused by different vagally-mediated mechanisms.     

Synthesis of human angiotensinogen (1-17) containing one of the putative glycosylation binding sites and its hydrolysis by human renin and porcine pepsin

The N-terminal heptadecapeptide of human angiotensinogen (Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu-Val-Ile-His-Asn-Glu-Ser-Thr-NH₂), with the C-terminal carboxyl group amidated, was synthesized in order to study the role of Asn-Glu-Ser, a putative carbohydrate binding site, on the hydrolysis by human renin. The synthesis was performed by fragment condensation using the Honzl and Rudinger azide procedure. In our conditions for azide segment condensation, histidine racemization was demonstrated to be negligible for most of the condensation reactions. Human renin liberates angiotensin I from h-angiotensinogen (1-17)-NH₂ with a K_m value of 3.4 × 10^?5m , at pH 7.3 and 37° being similar to h-angiotensinogen (1-13), an analog without the carbohydrate binding site. However, the V_max value of 4.1 × 10^?9mol/G.U. min is one order of magnitude higher. Porcine pepsin was demonstrated to cleave preferentially Leu¹⁰-Val¹¹ bond and, surprisingly, His⁹-Leu¹⁰ as well.     

Right Side Implant of the Unipolar Single Lead Defihrillation System

The active can defibrillator has been designed for implantation in the left prepectoral region. Whether this system can be successfully implanted on the right side is unknown. We describe six cases in which placement of the unipolar single lead defibrillation system was successfully attempted in the right prepectoral region due to impediments on the left side. The mean age of the patients was 62 ± 12 years. Five patients had is–chemic heart disease and one idiopathic dilated cardiomyopathy. The endocardial defibrillation electrode was placed in the right ventricle through the right subclavian vein and positioned at the apex in two patients and in the septal position in four patients. Defibrillation threshold testing was performed using a step-up/step-down protocol beginning at 12 J with 3-J increments or decrements. Defibrillation threshold was defined as the lowest energy of the first shock able to terminate ventricular fibrillation. The generator models used were the Medtronic 7218C in 1 patient, the Medtronic 7219C in 3 patients, and the Ventritex Cadet 115 AC in 2 patients. The mean defibrillation threshold was 15 ± 3 J. The defibrillation thresholds were retested at 1,3, and 6 months, and showed no significant change in five patients but decreased from 15 J to 12 J in one patient. The presence of impediments on the left side should not preclude attempts to place the unipolar active can system in the right prepectoral region.     

Koch's Triangle in Pediatric Age: Correlation with Extra- and Intracardiac Parameters

The atrioventricular node is situated in the lower atrial septum, at the apex of the Koch's triangle. The dimensions of the Koch's triangle are studied in adult humans, while no data exist about tbem in pediatric age. the knowledge of the dimensions of Koch's triangle in childhood is very important for safe and correct application of radiofrequency energy during transcatheter ablation. The dimensions of Koch's triangle were determined in 69 human pediatric hearts. the median age of the children was 3 months. with a range from 1 day to 14 years, 30 were female and 39 were male. Relations between body weight (extracardiac parameter) and tricuspid valve diameter (intracardiac parameter) were determined in all hearts to sbow morpbometric modifications with growth. the distribution of body weight was not Gaussian and no correlation could be obtained between Koch's triangle dimensions and body weight. However, it was possible to identify that the mean ratio between the cathetus of the Koch's triangle corresponding to the annulus of the tricuspid valve and the tricuspid valve diameter was 0.45 ± 0.16, with a highly significant correlation coefficient (r = 0.653, P < 0.001). Therefore, by knowing: (1) the diameter of the tricuspid valve, and (2) the constant ratio between the cathetus of the Koch's triangle and the tricuspid valve diameter, it is possible to calculate the lengtb of the segment of the tricuspid annulus along wbich the transcatheter application of radiofrequency current can be applied to ablate the slow-pathway, tbus reducing the risks of damage of the atrioventricular node.     

Hormonal and metabolic characteristics of geneticall obese Zucker and dietar obese Sprague-Dawle rats

Abstract. The endocrine-metabolic plasma pattern and the capacit of isolated perfused livers to produce triglcerides and ketone bodies have been studied in geneticall and diet-acquired obese rats (Zucker and Sprague-Dawle obese rats), and in control groups of the same strains.
An increased plasma insulin/glucagon molar ratio with hperinsulinaemia and hpoglucagonaemia was associated with hpertriglceridaemia, normal ketonaemia, elevated free fatt acids and normal or slight hperglcaemia in obese rats.
During oleate perfusion, the livers of Zucker and Sprague-Dawle obese rats showed an increase in triglceride output and liver triglceride content. The ketone bod output as well as the mitochondrial carnitine palmitol transferase activit were normal or slightl decreased.
In our rat population, a positive correlation between the insulin/glucagon molar ratio and triglceride output has been found.